- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Hosseini, H., Sameri, S., Das, D., Materna-Reichelt, S., Stojanovic Guzvic, N., Wöhrl, L., Hoffmann, M.Cancer cell plasticity, primarily mediated by the process of epithelial-mesenchymal transition (EMT), plays a critical role in promoting therapeutic resistance, tumor heterogeneity, and metastasis. EMT-mediated plasticity enables cancer cells to undergo molecular and phenotypic changes, which alter their invasiveness and resistance to treatments. This study aims to develop a quantitative, high-throughput system to assess EMT-mediated plasticity, which can inform therapeutic strategies for metastatic cancers. To accomplish this, we developed Plastimos, a semi-automated imaging analysis pipeline. This framework utilizes time-series images […]
- by Mollaheydar, E., Saboury, B., Rahmim, A., Cytrynbaum, E. N.Purpose: Radiopharmaceutical therapies (RPTs) are showing significant value in targeting various forms of cancer; meanwhile, as an emerging paradigm there is significant room for optimization of RPTs. We developed a computational model towards improving therapeutic strategies via modification of dosage and timing of RPT injections. Methods: Our model simulates tumor growth, the pharmacokinetics of RPTs, and the radiobiological impact of radionuclide decay through energy deposition on tumor tissue. Specifically, we use the Hybrid Automata Library (HAL) to simulate tissue con- […]
- by Sergounioti, A., Alonaris, E., Rigas, D., Kalles, D.Background: Understanding heterogeneity in sperm motility requires tools capable of capturing both dynamic patterns and interpretable structure. Symbolic encoding methods offer a novel way to represent motion trajectories through discrete motifs. Objective: This study explores whether symbolic time-series representations can uncover latent structure in sperm motility data, focusing on patterns of symbolic monotony and entropy. Methods: We applied Symbolic Aggregate approXimation (SAX) to 1176 sperm trajectories and computed motif entropy and dominance across multiple parameterizations (a = 3-7, k = […]
- by Kurgan, N., Kjaergaard, J., Jespersen, N. Z., Diez-Obrero, V., Moreno-Justicia, R., Heywood, S. E., Lindqvist, C. B., Ottander, L., Samodova-Sommer, D., Nielsen, N. S., Durrer, C. G., Ried-Larsen, M., Rasmussen, S., Loos, R. J. F., Smit, R. A. J., Pedersen, B. K., Deshmukh, A. S.Physical activity improves health, yet the molecular mechanisms remain partially understood. This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over 3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific exercise signatures with tissue and disease atlases, we delineated the contribution of tissues and associations to various diseases. Network analysis across body fluids elucidated coordinated remodeling in the extracellular matrix and immune activation orchestrating exercise-induced networks. […]
- by Saucier, D., Jiang, X., Rajendran, D., Ravishankar, R., Butler, E., Marchetto, A., Kurmasheva, R., Gruenewald, T., Amatruda, J., Danuser, G.Organotropism results from the functional versatility of metastatic cancer cells to survive and proliferate in diverse microenvironments. This adaptivity can originate in clonal variation of the spreading tumor and is often empowered by epigenetic and molecular reprogramming of cell regulatory circuits. Related to organotropic colonization of metastatic sites are environmentally-sensitive, differential responses of cancer cells to therapeutic attack. Accordingly, understanding the organotropic profile of a cancer and probing the underlying driver mechanisms are of high clinical importance. However, determining systematically […]
- by Alexandris, A. S., Yi, J., Liu, C., Belamarich, J., Alam, Z., Vats, A., Peng, A., Welsbie, D. S., Zack, D. J., Koliatsos, V. E.The central nervous system is characterized by its limited regenerative potential, yet striking examples of functional recovery after injury in animal models and humans highlight its capacity for repair. Little is known about repair of pathways/circuits after traumatic brain injury (TBI), which results in disruption of connectivity. Here we utilize a mouse model of diffuse traumatic axonal injury (Impact-acceleration TBI) in order to explore, for the first time, the evolution of structural and functional changes in the terminal fields of […]
- by Furukawa, T., Yamane, F., Takeuchi, R., Ohira, T., Toyota, K., Miyazaki, T., Tsutsui, N.In decapod crustaceans, insulin-like androgenic gland factor (IAG) is a well-known peptide hormone produced by the androgenic gland, a male-specific endocrine organ. In certain species classified within Pleocyemata, experimental manipulation of IAG signaling has successfully altered both internal and external sexual characteristics, leading to sex reversal. Therefore, IAG is considered a key regulator of male sexual differentiation and maturation and is thought to be a crustacean androgen. In the kuruma prawn Marsupenaeus japonicus (Dendrobranchiata), an important fishery species in Japan, […]
- by Lund, V. K., Chirco, A., Caliari, M., Larsen, A. H., Gether, U., Madsen, K. L., Wierer, M., Kjaerulff, O.Neuropeptide-containing dense core vesicles (DCVs) are generated in the neuronal cell body and circulate throughout the axonal arbor to supply distal release sites. This circulation depends on the anterograde kinesin-1 and kinesin-3 motors and the retrograde dynein-dynactin motor. While kinesin-3 is recruited to DCVs with the aid of the small GTPase Arl8, it is unclear how dynein and kinesin-1 are recruited and regulated. Here we show that DCV motility in Drosophila (fruit flies) depends on the dynein and kinesin-1 adaptor […]
- by Doricchi, F., Scozia, G., Pinto, M., Lozito, S., Lo Presti, S., Pazzaglia, M., Silvetti, M., Lasaponara, S.To compensate for its sensory intangibility, humans often rely on spatial metaphors, gestures, and visual tools to represent the passage of time. These spatial tools, i.e. heuristics, range from everyday practices, such as directional hand gestures to indicate past or future events, to more abstract scientific conceptualizations such as the curving of space-time in the theory of relativity. Despite this widespread spatialization of time, it remains unclear to what extent space is an inherent component of the neural representation of […]
- by Luo, Z., Tobias, P., Singh, L., Dong, C., Martino, A. M., Quecine, M., Massola Junior, N. S., Silva, L. C. A., Li, J., Singh, S., Zhang, Z., Jones, A., Park, R. F., Schwessinger, B., Edwards, R., Boufleur, T.Rust diseases on plants are caused by fungi in the order Pucciniales. Typically, rust fungi have narrow host specificity however the pandemic biotype of Austropuccinia psidii has an unusually broad host range causing disease on over 480 myrtaceous species globally. We assembled and analysed a fully phased chromosome-level genome for the pandemic A. psidii and addressed key outstanding questions of its infection biology. Our research revealed a conserved rust fungal karyotype of 18 haploid chromosomes, in line with fungi for […]
- by Gao, W., Gao, B., Wang, S., Wu, D., Mei, P., Geng, L., Li, C., Li, Y., Liu, X., Pan, J., Huang, J., Deng, Y., Chen, X., saiyin, H., Yu, H., Li, S., Zhang, Q., Xu, B., Huang, F., Ming, C., Wu, H., Li, J.Alzheimer disease (AD) is a devasting neurodegenerative disorder characterized by beta-amyloid formation, further exacerbated by RIPK1/RIPK3 necrosome-induced programmed necrosis (necroptosis). We previously showed that the RIPK1/RIPK3 necrosome forms a functional amyloid complex using its RIP homotypic interaction motifs (RHIMs). Here, we discovered that the core RIPK1/RIPK3 necrosome shares strikingly structural similarity to the C-terminal region of beta-amyloid (Ab-42), and the RHIM-derived tetrapeptides (IQIG or VQVG) directly inhibit Ab aggregation, disassemble preformed Ab fibrils (PFFs), and reduce RIPK1 polymerization. Also, the […]
- by Duan, Z., Yang, R., Lai, T., Jiang, W., Zhang, J., Chen, B., Liao, L.Pseudoalteromonas has been used as a model system to study cold adaptation and is of widespread interest in biotechnology and ecology. To explore its physiological responses to extreme cold, uncover functional genes, and clarify their ecological roles, efficient genetic tools are essential. However, existing genetic manipulation methods in Pseudoalteromonas rely on traditional homology-based recombination, which is inefficient and time-consuming. Consequently, improving editing efficiency is crucial for advancing both basic research and applied potential. Here, we introduced the CRISPR/Cas9 system into […]
- by Rietjens, R. G. J., Manzato, B., van den Berg, B. M., Mahfouz, A., Giera, M., Dumas, S. J., Wang, G., Rabelink, T. J.After acute kidney injury (AKI), the persistence of failed repair proximal tubule (FR-PT) cells is postulated to hamper kidney regeneration and increase the risk of chronic kidney disease. This fibrotic shift likely depends on microenvironmental interactions, which remain largely unstudied. To investigate this, we mapped the spatial metabolic architecture of post-ischemic kidneys using an untargeted semi-quantitative spatial metabolomics (qMSI) approach, integrated with high-resolution spatial transcriptomics. Unsupervised neighborhood clustering of qMSI data revealed distinct microenvironments. Lipidome profiles identified diffusely spread areas […]
- by Trout, E., Palomo, L., von Recum, H. A., Eppell, S. J.Dental implants commonly suffer from chronic peri-implantitis arising from infection and inflammation at the abutment/gingiva interface, primarily because they fail to replicate the collagen-rich soft tissue interface between natural teeth and the jawbone. Current treatment strategies involve frequent administration of systemic antibiotics and collagenase inhibitors which complicates clinical management. A localized controlled drug-release approach may offer a way to simplify this clinical management. In this study, we investigate doxycycline loading and release from a collagen hydrogel containing entrapped oligomers of […]
- by DiNardo, A. L., Kurhanewicz, N. A., Wilson, H. R., Berg, V., Libuda, D. E.Germ cell proliferation and proper genome inheritance are critical for maintaining fertility through generations. To promote proper germ cell development, small RNA pathways employ Argonaute proteins (AGOs) to modulate gene expression and protect against deleterious genomic elements while not silencing against self. Here we identify sexual dimorphisms in localization and function of protein structural features of the Argonaute WAGO-1 that affects sex-specific gene regulation during C. elegans germ cell development. During meiotic prophase I progression, we find that germ granule […]
- Lysosomal stress induces amyloid-β aggregate release and reactive transformation in human astrocytesby Goldsworthy, S., Fertan, E., Dyal, P., Domoney, S., Livesey, F., Klenerman, D., Patani, R., Hung, C.Astrocytes are essential for brain homeostasis and are involved in amyloid-{beta} (A{beta}) clearance, but whether they can produce and release A{beta} aggregates remains unclear. Using human iPSC-derived astrocytes, we show that astrocytes cell autonomously generate small, diffusible A{beta} aggregates under baseline conditions. By combining ultrasensitive single-molecule imaging (DNA-PAINT) and immunoassays, we detect intracellular aggregates and their release into the media. Notably, lysosomal membrane damage induced by L-leucyl-L-leucine methyl ester (LLOMe) significantly increases A{beta} aggregate secretion without altering their size or […]
- by Su, D., Liu, G.T cell receptor-engineered T (TCR-T) cell therapy holds distinct advantages over chimeric antigen receptor (CAR)-T cell therapy in treating solid tumors by exploiting intracellular targets through MHC-mediated antigen presentation. Despite this potential, only one TCR-T therapy has received FDA approval to date. A key challenge lies in chain mispairing between exogenous therapeutic TCR chains and endogenous TCR chains, which compromises membrane localization efficiency and elevates off-target toxicity risks. While multiple engineering strategies have been developed to enhance TCR surface expression, […]
- by Ben Dhaou, C., Al-Yafeai, Z., Cruz-Marquez, G. A., Scott, M. L., Pearson-Gallion, B., Cockerham, E., Li, H., Peretik, J. M., Hong, Y., Dhanesha, N., Yurdagul, A., Rom, O., Bhuiyan, M. S., Orr, A. W.Atherogenic endothelial activation arises from both the local arterial microenvironment–characterized by altered extracellular matrix composition and disturbed blood flow–and soluble proinflammatory stimuli such as oxidized low-density lipoprotein (oxLDL). Fibronectin, a provisional extracellular matrix protein enriched at atheroprone sites, enhances endothelial activation and inflammation triggered by oxLDL and disturbed flow. Although endoplasmic reticulum (ER) stress contributes to vascular dysfunction, the role of matrix composition in regulating ER stress remains unknown. We show that oxLDL and disturbed flow induce ER stress selectively […]
- by Whyte, C. J., Wilson, H. R., Shine, J. M., Alais, D.Visual rivalry paradigms provide a powerful tool for probing the mechanisms of visual awareness and perceptual suppression. While the dynamics and determinants of perceptual switches in visual rivalry have been extensively studied and modeled, recent advances in experimental design – particularly those that quantify the depth and variability of perceptual suppression – have outpaced the development of computational models. Here we extend an existing dynamical model of binocular rivalry to encompass two novel experimental paradigms: a threshold detection variant of […]
- by Izarra, M. L., Perez, W. G., Vasquez, E. F., Perez, G. E., Gamboa, S., Andrade-Piedra, J., Flores, B., Montejo, L., Sanders, A., Kreuze, J. F.Late blight caused by Phytophthora infestans poses a significant global threat to potato and tomato cultivation with profound historical and ongoing impacts on food security. In Central America, particularly in Guatemala and Honduras, the disease has intensified over the last decade, possibly due to favorable climatic conditions and changes in local pathogen populations. This study identified four distinct clonal lineages of the A2 mating type, US7A2, US8A2, and 13A2, and a newly identified lineage exhibiting genetic variation. Mitochondrial haplotype analysis […]